Partially disturbed lamellar granule secretion in mild congenital ichthyosiform erythroderma with ALOX12B mutations.

Congenital ichthyosiform erythroderma (CIE) (OMIM 242100) is a major type of autosomal recessive congenital ichthyosis (ARCI) showing generalized scaling and erythroderma without blister formation. Mutations in ALOX12B (OMIM 603741), encoding 12R-lipoxygenase (LOX), were identified in patients with CIE in 2002. To date, several ALOX12B mutations have been reported in CIE families. LOXs are a family of nonhaem, iron-containing dioxygenases which catalyse dioxygenation of fatty acids with one or more (Z,Z)-1,4-pentadiene moieties. Three members of the human LOX family, 15-LOX-2, 12R-LOX and eLOX-3, are preferentially expressed in the skin. The 12R-LOX pathway leads to hepoxilin B3 and trioxilin B3 resulting in 20-carboxy-trioxilin A3, which is thought to be a key biological regulator in the skin. 12R-LOX deficiency results in a CIE phenotype in humans and in mice. We report that a Japanese patient with CIE, harbouring one previously unreported ALOX12B mutation p.Arg442Gln and another known mutation p.Arg432X, showed partially disturbed secretion of lamellar granule (LG) contents in the epidermis.